The long-term goal of this research is a better understanding of what factors determine the addictive liabilities of drugs. Using morphine as the prototype agent, experiments are planned to analyze further the neuropsychological mechanisms of morphine addiction and dependence in rats. Specific experimental problems include determination of morphine's neuroanatomical site(s) of action(s), the neuropharmacological basis of morphine's action(s) and of morphine antagonism, and the relationship of morphine analgesia to morphine addiction. Intracerebral administration of naloxone, experimental brain damage, inhibitors of neurohumoral synthesis and other agents with relatively specific modes of action will be used as tools to facilitate study of possible mechanisms of morphine's actions. Although several behavioral procedures will be utilized in various parts of this research, emphasis will be placed on the determinants of intravenous drug self-administration. Neurochemical correlates of self-administration behavior and of drug-lesion interactions will be sought when appropriate. Comparable studies with methadone, meperidine and d-amphetamine will be begun in order to determine the generality of previous findings involving morphine will respect to whether a common neuronal substrate mediates drug reinforcement. The possibility that experience with one agent (e.g., d-amphetamine) will predispose to addiction to another agent (e.g., morphine) will also be investigated.